JPH01107737A - Optical fiber probe connector for physiological measuring apparatus - Google Patents

Abstract

PURPOSE: To obtain an optical fiber probe connector of a physiological measuring instrument by providing this connector with a sealed annular passage in the longitudinal direction which is packed with an optically active chemical indicator pressed to its closed end and in which the balance is a socket cavity opened for the purpose of an optical fiber core. CONSTITUTION: The connector 10 is a cylindrical member consisting of a sheath 11 which forms the cavity packed with the optically active chemical indicator material 13 and an end cap 12. The connector has an internal passage cavity 14 which is an annular groove acting as a female socket for the terminal strand of the optical fiber. The diameter of the cavity 14 snugly houses the optical fiber and embodies the contact and optical coupling with the optically active material 13 capsulated at a boundary joint part 15. The sleeve connector 10 is a gaseous oxygen sensor and the indicator material consists of oxygen extinction fluorescent dyes 16 dispersed into a polymer matrix 17. The sheath 11 consists of a gas permeable material, such as hydrophobic expanded polypropylene and silicone polymer, as the armor of the oxygen sensitive fluorescent dye material 13.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a fiber optic probe device for implantation within the body for the measurement of body fluid components, and more particularly relates to the physiological measurement of oxygen and glucose in blood or tissue. .

Physiological oxygen and glucose measurements are important for many reasons. During certain medical procedures, such as cardiopulmonary bypass heart surgery, the benefits of optical measurement of blood oxygen saturation levels are obvious. Equally important are physiological measurements of glucose in blood tissue or serum, which are indicative of metabolic dysfunctions such as diabetes.

Fiber optic devices for measuring blood oxygen saturation are well known. Osdrowski et al.'s U.S. patent cylinder 3,8
No. 07,390 describes blood oxygenation in human blood by insertion of a catheter tip into the cardiovascular system of a living body.

A fiber optic catheter for in-vivo monitoring of saturation is disclosed.

US Pat. No. 3,542,662 to Hicks et al. describes a live electrode for use in measuring glucose in blood and serum. In this patented device, an enzymatic reaction is combined with an electrode process.

A glucose electrode consisting of a membrane of immobilized glucose oxidase has been described. When the enzyme electrode comes into contact with a physiological solution or tissue, glucose and oxygen diffuse into the enzyme layer, generating a corresponding outflow of hydrogen peroxide and gluconic acid. The relationship between the oxygen saturation level and the amount of gluconic acid and peroxide present in the system is then calculated,
The amount of glucose is then checked.

Haas U.S. Pat. is disclosed. The catheter includes a semi-permeable wall member for excluding the ingress of blood fluids but allowing the passage of blood gases therethrough. The intensity of the reflected visible light beam entering the fiber optic bundle corresponds to the partial pressure of oxygen gas in the bloodstream when compared to the intensity of the incident beam.

The present invention relates to fiber optic devices for in vivo physiological measurements of oxygen and glucose by chemical sensors using luminescent light mechanisms. Oxygen quenching of fluorescent compounds is described in US Pat. No. 3,612.866 by Stephens.
It is disclosed in issue, and it contains a measurement device for oxygen content in the liquid or gas. The indicator mechanism is based on the chemiluminescence quenching effect of gaseous oxygen on aromatic fluorescent compounds. In addition, U.S. Pat. No. 4,003,707 to Rahas et al. describes an optical device for measuring physiological oxygen in which the indicator element is pyrenebutyric acid, a fluorescent dye that is quenched by oxygen molecules during use. . All of these devices are complex and do not allow for the dimensions of the measuring device and the replacement of the dye indicator system.

U.S. Pat. No. 4,476,870 to Beaterson et al.
Implantable optical fiber P consisting of two strands of optical fiber terminating in a jacketed chemical indicator system
O□Describe the physiological probe.

The indicator element contains a luminescent oxygen-quenching dye, such as berylene dibutyrate, on an inorganic adsorbent, all packed within a tube or envelope of gas-permeable polymeric material. Light is introduced through one strand,
This light excites the jacketed dye, causing it to fluoresce. The fluorescent and scattered light then exits through other optical fiber strands to a measurement device that indicates the level of oxygen quenching of the dye.

Although Peterson et al.'s device is small and flexible for convenient in-body use, it is important to note that the adsorbed dye is ultimately lost by elution into the fluid system during use, thereby requiring replacement of the entire structure. The disadvantage of needing it is 7.

Each of the systems has advantages and disadvantages when applied to particular situations. In one or more of the systems, expensive and complex equipment is required, especially in the case of glucose sensors. Furthermore, even in simple compact structures, such as the device of Beaterson et al., the optics are integral and the entire device must be replaced when the chemical sensor becomes unusable. Therefore, there is significant interest in finding relatively simple physiological light measurement devices in which the chemical sensor element can be easily replaced.

The present invention is an advancement in the technology of physiological fiber optic sensors for the physiological measurement of body fluids, and the unique combination of novel features overcomes the inadequacies and shortcomings of previous similar devices. Overcome a lot of things. Specifically, a specially designed disposable chemical sensor comprising a fiber optic probe attachment is provided, acting as a fiber optic end sensor over which body fluids flow when they are being monitored. In addition, a novel chemical sensor sleeve design is employed to provide a novel dual probe catheter assembly for physiological glucose and oxygen measurements.

The device of the present invention provides a means to readily obtain photometric analysis of body fluids with conventional photometric analysis equipment, including catheters intended for insertion into the bloodstream or tissue of a patient. The device therefore includes a chemical sensor tip consisting of a removable sleeve connector containing a reversible chemical indicator sensitive to specific components of body fluids.

The sleeve connector is optically and physically coupled to the optical fiber that is the source of the input and output illumination to the chemical indicator tip. The optical fiber is connected to photometric analysis equipment that interprets changes in the chemical indicator substance caused by reactive components of specific body fluids that impinge on the sensor tip. During use, the probe device is desirably disposable for health and safety reasons, since it is essential that the indicator sleeve tip is immersed in body fluids as the fluid stream in the catheter. The indicator sleeve of this device can be conveniently and easily replaced without interrupting use.

Lesson 2 The invention is illustrated in the accompanying drawings.

FIG. 1 is a longitudinal cross-sectional view of an optical sensor-sleeve connector of the present invention having a chamber containing a chemical indicator for a body fluid component.

FIG. 2 shows an optical sensor employing a multilayer envelope for a chemical indicator to be useful in measuring physiological glucose.
FIG. 7 is a longitudinal cross-sectional view of another specific example of the sleeve connector.

FIG. 3 is a cross-sectional view showing the end face of the second chemical indicator portion.

FIG. 4 is a partial front view of a dual probe catheter that is another embodiment of the invention and uses first and second sleeve connector structures.

Although this optical sensor has its primary use in measuring physiological oxygen saturation, it can be used to measure other physical phenomena that exhibit similar behavior and meet the criteria developed here. can also be applied satisfactorily. Devices for physiological oxygen and glucose measurements will be used as illustrative examples and preferred embodiments.

FIG. 1 illustrates a longitudinal section of an optical sleeve sensor connector element 10 of the present invention. The connector IO includes a sheath 11 and an end cap 12 that form a cavity filled with an optically active chemical indicator material 13, typically including a dye or luminescent material that interacts with physiological components in a biological environment. It is a cylindrical member. Also shown is the internal passageway cavity 14, which is an annular groove that acts as a female socket for the terminal strand of optical fiber (not shown). The diameter of the cavity 14 is proportionate or proportionate to the core of the optical fiber so as to snugly accommodate the optical fiber and thereby provide abutment and optical coupling with the encapsulated optically active material 13 at the interfacial junction 15. It has virtually the same dimensions. The tip of the emitting fiber must be firmly pressed against the chemical indicator material at the interfacial joint 15.

As shown, the sleeve connector 10 is an oxygen gas sensor and the indicator material consists of an oxygen-quenching fluorescent dye 16 dispersed in a polymer matrix 17.

In addition, as an outer lining for the oxygen receptor fluorescent dye material 13,
The sheath 11 is comprised of gas permeable materials such as well known hydrophobic expanded polypropylene and silicone polymers.

Tip 12 is the element of this structure that faces and contacts physiological fluid flow when in a catheter encountering blood, tissue or serum, and must also be of gas permeable material. Although shown as a separate element, the end cap 12 is integral to the sheath and can be of the same material or of a different gas permeable composition. If end cap 11 is the same gas permeable material as sheath 11, it is preferably in a thinner form, such as a membrane.

A suitable example of an oxygen-quenching dye material to be used in the indicator element 13 is disclosed in U.S. Patent Application No. 071047,6 by Oviatt et al.
90 and Hsu et al. 071000.537, respectively. Other examples include the fluorescent dye pyrenebutyric acid in bis-2-ethylhexyl phthalate. Still other examples include perylene and benzoperylene embedded in room temperature vulcanizable silicone polymers. Since this fiber optic sleeve connector is replaceable, it is not necessary for the indicator oxygen-quenching fluorescent dye to be embedded or chemically bonded to the polymer matrix to avoid dye elution. Dyes or luminescent materials can therefore be adsorbed or mixed into the polymeric binding material.

The polymeric matrix of the sheath material 11 and indicator element 13 can be comprised of any gas diffusive hydrophobic material, such as silicone polymer, polyester or any gas permeable synthetic plastic material. A preferred sheath material 11 is manufactured by Celanese Corporation under the trademark CELGA.
Porous expanded polypropylene tubing sold under RD. Other preferred polymers include tetrafluoroethylene and polydimethylsiloxane.

FIG. 2 shows another embodiment of the present invention in the form of a multilayer tubular glucose indicator sleeve 20 of the present invention in which 24 is the same fiber optic probe socket groove. Similarly,
The female socket groove 24 ends at 25 and the first
It interfaces with a chemical indicator filling portion which is the same as chemical indicator element 13 in the figure. The sheath or sheath portion designated as 21 corresponds functionally to sheath 11 of FIG. 1, but includes a multilayer sheath for the chemical indicator 23. Immediately surrounding indicator portion 23 is a thin cylindrical wall of gas permeable material such as expanded polypropylene, and is designated herein as inner layer 28 .

Coated over inner layer 28 is sandwich layer 29, which is a glucose conversion layer and includes glucose oxidase dispersed in a polymer matrix or cross-linked with glutaraldehyde. Overlying and jacketing the entire cylindrical portion of glucose connector sleeve 20 is an upper layer 28 of gas permeable material such as expanded polypropylene. End cap 22 of element 20 is the same as described for element 12 of FIG. Optical fiber core and cavity 2 for forming an optical interface connection with the encapsulated chemical indicator 23 at junction 25
The sliding female interaction with 4 is the same as the connection description given for FIG.

The tube shape of FIG. 2 is shown more clearly in FIG. 3, where a cross-sectional view showing the socket cavity 24 of the multilayer cladding 21 is shown. As can be seen, the cavity 24 and indicator material (not shown) are surrounded at the outer periphery by the inner and upper layers 28 and the sandwich layer 29 of the glucose oxidase catalyst. It is this multi-tube structure that enables efficient operation of the dual probe glucose sensor catheter described below.

The oxygen gas indicator sleeve of FIG. 1 is manufactured in the following manner. Cut 2 cm lengths of 240 micron diameter CELCARD expanded polypropylene hollow tubing. Ru
An oxygen-quenching dye indicator composition consisting of (4,7-diphenyl-1,10-phenanthroline) ICl3 and an uncured polydimethylsiloxane crosslinked binder is provided in a syringe. The annular passage of the polypropylene tube is filled 3/4 with the dye composition and cured. Trim one open end of the tube with a razor blade to expose a continuous circular cross section of polypropylene and dye indicator. The continuous end piece is dipped into a portion of polydimethylsiloxane sealant and allowed to cure, thereby forming a membrane end cap on the tube element, corresponding to element 12 of FIG. A fiber optic sleeve connector is provided having an open cavity socket and a closed passageway having an oxygen indicator dye composition contained therein.

The socket passage of the sleeve connector (cavity 1 in Figure 1) manufactured with a strand of optical fiber of approximately 230 microns
4) Insert the dye indicator part (first
Optical coupling is completed at the interface of element 13 in the figure (15 in Figure 1). Optionally, and preferably, a strand of optical fiber can be connected to the socket passageway 14 after insertion and prior to curing of the dye composition to form an integral and non-removable 6s optical probe connection. In this embodiment, the optical fiber can be in direct contact with the uncured dye composition to form a fused optical interface series (element 15 in FIG. 1) with the dye indicator portion of the connector.

When using this operation, a gas permeable end camp is applied after coupling the optical fiber to the sleeve connector.

To make the second glucose indicator, 44040 Miflon CELGARD polypropylene tubing is prepared and cut with a razor into approximately 4 inch segments.

For the immobilized enzyme layer, solutions of glutaraldehyde, glucose oxidase, catalase, and bovine serum albumin are prepared in a conventional manner using a mixed acetate buffered solution of glutaraldehyde. Bovine serum albumin (BS
A) Enzyme immobilization of glutaraldehyde in a matrix was carried out by Thomas et al.
al., Biochimie.

Vol, 55. pp, 229-244.
Monoenzymatic MoclelMemb
It was carried out by the technique described in Rane.

The enzyme solution is then placed in the syringe and added by needle to the annular passage of the polypropylene tube so as to completely fill the inner space. Prior to curing of the enzyme solution, an unconnected oxygen sensor sleeve made in the manner described above is inserted into the large tube and curing of the enzyme layer is completed.

This results in a glucose sensor sleeve connector according to FIG. 2 that can be physically and optically coupled to an optical fiber strand. Again, as with the oxygen sensor fabricated above, an integrated oxygen sensor fiber optic probe can be fabricated and inserted into a large polypropylene tube with an uncured enzyme layer to form an integrated glucose sensor probe. can.

As indicated, the sensor sleeve connector elements of FIGS. 1 and 2 are gas permeable and filled with a fluorescent dye or luminescent material, thereby forming the fluorescent transducers 13 and 23. It is formed from a tube. The transducer is such that incoming light causes excitation of the fluorescent indicator with re-emission of light through the optical fiber. Since the degree of oxygen quenching affects the fluorescent material, the re-emitted light can be correlated to the oxygen concentration in the indicator and its measurement.

In operation, the fiber optic glucose sensor of FIG. 2 is contacted with blood or serum containing a certain concentration of glucose and oxygen.

Both glucose and oxygen diffuse through the gas permeable layer of sheath 21, but only oxygen diffuses through the hydrophobic end cap 2.
can be diffused through 2.

Oxygen continues to diffuse into the fluorescent dye polymer layer where it quenches the oxygen-quenched fluorescent dye. Glucose and oxygen in the fluid come into contact with the immobilized glucose oxidase layer 29 which contains the catalyst and thus promotes the following reaction.

Gluconic acid + H,0 (2) H! O! Ten catalase □→H! O+1/2
Some of the oxygen that diffuses through the 0x sleeve connector 20 is consumed by the enzyme-catalyzed glucose and e-reactions in layer 29 and is therefore not available for detection by the oxygen-quenching fluorescent dye in 23. In order to calculate the accurate concentration of glucose, an oxygen sensor is needed as a reference sensor to read the oxygen concentration that would have been detected if the enzymatic reaction had not occurred in the glucose sensor of FIG. With a suitable compensation factor, the difference in detected oxygen will be proportional to the glucose concentration so calculated.

However, for a system to provide useful results, glucose concentration, not oxygen concentration, must be the limiting factor. This reaction is stoichiometrically limited depending on which component is present in the lowest concentration, so the trademark T
A thin membrane made of medical grade polyurethane, commercially available from Thermedix under the ECOFLEX designation, limits the flux of glucose into the glucose sensing portion of the dual probe device, rather than the flux of oxygen. is placed around the outer sheath of the glucose probe. This method makes it possible to ensure that the desired analyte glucose is always present as a limiting species.

The optimum application for the sleeve connector illustrated in FIGS. 1 and 2 is as a dual probe glucose oxygen sensor. Fourth
The figure illustrates a novel dual probe catheter assembly 30 that uses the sleeve connector of the present invention. There the essential working parts of the dual probe catheter assembly 30 are shown, two optical fibers 31, 32 are drawn and connected to a spectrum analyzer (not shown), and the optical fiber strands enter the housing head 33. In front of it is sheathed or covered. As shown, the two fibers are drawn together through an orifice (not shown) and housed by a tubular catheter 34, shown separately in the figures. The tips or terminals 35 and 36 of the drawn dual strands of optical fiber are optically coupled to the fluorescent oxygen and glucose sensor elements shown in FIGS. 1 and 2 in the manner previously described.

The sleeve sensor is then housed in a tubular catheter 34 that is secured to the housing 33. Tubular catheter 34 is then inserted directly into the human or animal body, so that the oxygen and glucose sensor elements are in direct contact with the blood or serum to be analyzed. Terminal 3
The indicator elements attached to 5 and 36 are in direct contact with the specific blood or serum and affect the emitted light from the chemical indicator of the probe in the manner described above. Spectral data from each optical fiber strand is measured and analyzed for oxygen and glucose content of the sample indicated by the respective tubular end probe.

The optical mounting structure and optical probe structure of the present invention was selected because it can be conveniently manufactured in large quantities and provides a plurality of devices for optically measuring samples of material undergoing fiber optic probe analysis. Can be assembled with sensor. The various members of the optical mounting interface structure so produced can be used interchangeably. The uniform geometry of the optical fiber ensures optical coupling at the optical interface between the optical fiber and the chemical indicator element. The optical mounting interface structure of the present invention therefore has wide applicability in situations where multiple fiber optic measurements or analyzes must be performed accurately and rapidly.

It will be appreciated that the optical sleeve connector of the present invention allows conventional catheter-type input to photometric analysis equipment used continuously and repeatedly for photometric analysis of physiological components of body fluids.

The novel features considered characteristic of the invention are set out in detail in the claims.

The invention itself, however, both as to its construction and method of operation, together with additional objects and advantages thereof, will be best understood from the foregoing description of specific embodiments when read in conjunction with the accompanying drawings.

[Brief explanation of the drawing]

FIG. 1 is a vertical sectional view of the optical sensing sleeve connector of the present invention, FIG. 2 is a vertical sectional view of another example of the optical sensing sleeve connector, and FIG. 3 is a longitudinal sectional view of the chemical indicator portion of FIG. The cross-sectional view shown, FIG. 4, is a front view of a dual probe catheter using the sleeve connector of FIGS. 1 and 2. 10.20 is optical sleeve sensor connector, 11.2
1 is the sheath, 12.22 is the end cap, 13.23 is the chemical indicator material, and 14.24 is the cavity. FIC;, 4

Claims (10)

[Claims] (1) A tubular shape with a sealed longitudinal annular passage whose part is filled with an optically active chemical indicator abutting the closed end and the remainder is an open socket cavity for the optical fiber core. An optical fiber connector made of pods. (2) the pod is made of a gas-permeable polymer material;
The fiber optic connector of clause 1, wherein said chemical indicator is an oxygen-quenching fluorescent dye. (3) The fiber optic connector of clause 2, wherein the sheath further comprises a sandwich layer of immobilized glucose oxidase and an upper layer of gas permeable material. (4) The gas permeable polymer layer comprises polypropylene,
The optical fiber connector of item 3, which is a gas permeable polymer selected from the group consisting of tetrafluoroethylene and polydimethylsiloxane. (5) The optical fiber connector according to item 3, wherein the immobilized glucose oxidase layer contains glucose oxidase crosslinked with glutaraldehyde. (6) forming (a) an optical fiber core; (b) a sealed vertical annular passageway, the sealed portion of which is an optically active chemical indicator segment, and the remainder of the passageway around a sheath; A fiber optic probe sensor comprising a tubular sheath housing an optical fiber core to provide a physical connection between the optical fiber and the chemical indicator. (7) The fiber optic probe sensor of clause 6, wherein the sheath is comprised of a gas-permeable polymeric material and the chemical indicator is an oxygen-quenching fluorescent dye. (8) The fiber optic probe sensor of clause 6, wherein the pod further comprises a sandwich layer of immobilized glucose oxidase and an upper layer of gas permeable material. (9) The gas permeable polymer layer comprises polypropylene,
The optical fiber probe sensor of item 6, which is a gas permeable polymer selected from the group consisting of tetrafluoroethylene and polydimethylsiloxane. (10) The optical fiber probe sensor according to item 8, wherein the immobilized glucose oxidase layer contains glucose oxidase crosslinked with glutaraldehyde.